p-Value and power computations in multiple look trials

Abstract

This paper presents at an instructive level detailed design, decision and computational aspects of p-values and power for clinical trials in which interim looks at accumulating data are planned. Background theory and an application are presented. In addition, a definition of the term p-value, appropriate for a trial in which interim looks are planned is proposed. The definition is intuitively consistent with that for a fixed sample size trial. That is, the p-value reflects the strength of the data against the null hypothesis. For trials incorporating group sequential methods, the p-value at a particular look reflects the conditional nature of the data collected through that look on the data collected through earlier looks.